Medical diagnostic imaging has evolved as an important non-invasive tool for medical diagnosis. Nuclear magnetic resonance imaging (“MRI”) and computerized tomography (“CT”) are two of the most widely used imaging methods. MRI generally relies on the relaxation properties of excited hydrogen nuclei in water. When the tissues or organs to be imaged are placed in a powerful, uniform magnetic field, the spins of the hydrogen protons within the tissues or organs align along the axis of the magnetic field. Medical imaging technologies also include ultrasound, SPECT or positron emission technology (PET) scans.
Imaging diagnosis plays an important role in medicine because it facilitates the accurate localization and characterization of disease that is critical for therapeutic decision-making and for the overall outcome of patient management. Due to technical innovations, imaging technologies have become much more powerful and versatile.
Although diagnostic imaging may be performed without the administration of contrast agents, the ability to improve the visualization of internal structures, for example tissues and organs, and fluids has resulted in the widespread use of contrast agents. Contrast agents are used to highlight specific areas to increase the visibility of the area being studied. Contrast agents for MRI technology alter the relaxation times of tissues and body cavities where they are located and work by shortening the relaxation time of protons located nearby.
The use of injectable contrast agents in conjunction with imaging techniques has increased dramatically over the last decade. These currently used contrast agents are generally safe, however, they are associated with some undesirable side effects. These side effects are divided into four major areas: systemic reactions, cardiac effects, renal effects, and general vascular effects. There have been many attempts to develop new contrast agents, with a primary aim of lessening the adverse effects.
Despite improvements in spatial and temporal resolution of diagnostic imaging, it remains difficult to make an unambiguous diagnosis even with the use of contrast agents. This problem may be attributed to the fact that there is substantial overlap in imaging signals between both pathological and normal tissues. One approach to solve this problem is to develop more specific contrast agents that specifically concentrate in targeted organs or tissues.
The use of porphyrins over the past decades sparked an interest in the development of new compounds that exhibit targeting capabilities. However, problems related to many porphyrin based contrast agents include instability, discoloration, toxicity and slow clearance rates. Several patent applications such as WO 00/09169 and WO 02/38546 discuss various non-porphyrin contrast agents that exhibit some “targeting” abilities however, problems related the reproducibility of these compounds along with slow clearance rates and longevity of the compound within the patient continue to exist.
It is, therefore, desirable to provide a contrast agent having more desirable pharmacokinetic related clearance properties and minimized toxicity and/or side-effects.